Scott Letendre, M.D. is an Associate Professor of Medicine at UCSD and former K23 Career Development Award recipient. In the past decade, Dr. Letendre has led or collaborated on many publicly and privately funded translational research projects. His influential work has focused on the risk factors and treatment of HIV-associated neurocognitive disorder (HAND) in the US and international settings. During this period, he has also mentored more than 30 trainees in patient-oriented research, including graduate and medical students, post-doctoral researchers, and junior faculty. In the proposed K24 mid-career investigator award, Dr. Letendre will expand his mentoring of junior investigators and will focus his mentoring and his own research on three main objectives. Antiretroviral treatment of the nervous system: Dr. Letendre will mentor trainees on design and performance of HAND clinical trials and CSF pharmacology projects, particularly focusing on longitudinal projects that measure all drugs in an antiretroviral regimen to better understand how drug interactions and time influence virologic and neurocognitive outcomes. Biomarker correlates of disease and treatment: Dr. Letendre will mentor trainees on measurement and analysis of biomarker data with the goal of developing a clinically useful panel for screening, diagnosis, and prognosis of HAND. This work will be supported by new equipment purchased with funds from a recent S10 Shared Instrument Grant. Coinfections in HIV-infected individuals: Dr. Letendre will work with trainees on projects that evaluate the impact on the nervous system of latent or minimally symptomatic infections with pathogens such as Plasmodium, Cytomegalovirus, Toxoplasma, and hepatitis C virus. This work will particularly focus on Dr. Letendre's existing work in international settings. Dr. Letendre will mentor trainees using a multidisciplinary approach that includes regular direct engagement, participation in R25, T32, and K30 programs at UCSD, active participation in existing research projects, support for new research projects, and networking with other investigators. Dr. Letendre will also obtain training in mentoring and analysis of longitudinal data. In summary, this K24 award will secure protected time for Dr. Letendre to mentor trainees in neuroAIDS methods, including the responsible conduct of patient- oriented research. Dr. Letendre will coordinate his efforts with other UCSD resources, including the R25- funded International Research Fellowship in NeuroAIDS, the T32-funded Training in Research on Addictions in Interdisciplinary NeuroAIDS, and the CTSA-funded Clinical and Translational Research Institute.